1. Technical Field
The present invention relates to adamantane derivatives that are active as antiviral and anti-microbial agents against various organisms listed by the Centers for Disease Control as Category A, B and C pathogens. These compounds have been shown to be particularly active against the vaccinia virus.
2. Description of the Background Art
Adamantane, or tricyclo[3.3.1.13.7]decane, is a cycloalkane consisting of four cyclohexane rings arranged in an armchair configuration. Because of its symmetry, rigidity and stable structure, it is known as a desirable component for use in pharmaceutical compositions. Additionally, adamantane derivatives and resins have been investigated for use in optics, electronics and dental composites.
Adamantane derivatives are well known to have anti-viral and anti-microbial activity. Amantidine, believed to have been the first adamantane derivative to be used medicinally, is an adamantine that was modified by the addition of an amino group. It has been used primarily to combat various strains of influenza. Additional adamantane derivatives have been described. See generally U.S. Pat. No. 4,661,512. Adamantane derivatives have been used therapeutically in the treatment or prevention of Parkinson's disease, Borna disease, HIV1 and complications associated with diabetes, such as high intraocular eye pressure. Adamantane's mode of action remains largely unknown.
It has now been found that the adamantane derivatives disclosed herein have unexpectedly improved properties compared to other antiviral and antimicrobial agents. Specifically, the adamantine derivatives described herein have been shown to be active against the vaccinia virus, as well as other microorganisms classified by the National Institute of Allergy and Infectious Diseases as Category A, B and C pathogens. Vaccinia virus is associated with smallpox, which the Department of Homeland Security has designated a “material threat” to our national security. Thus, there is a need for agents that are effective at preventing or treating vaccinia related infections.